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DAD1  -  defender against cell death 1

Homo sapiens

Synonyms: DAD-1, Defender against cell death 1, Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1, OST2, Oligosaccharyl transferase subunit DAD1
 
 
 

Summary

This protein belongs to a complex called OST (oligosaccharyltransferase), which transfer the precursor N-glycan to a newly translated protein on its target sequence (usually a Asn-X-Ser/Thr motif, or a Asn-X-Cys)

 

Summary (from Uniprot)

DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggered apoptosis. DAD1 is believed to be a tightly associated subunit of oligosaccharyltransferase both in the intact membrane and in the purified enzyme, thus reflecting the essential nature of N-linked glycosylation in eukaryotes. [provided by RefSeq]
 

Disease relevance of DAD1

 

High impact information on DAD1

  • Two independently derived Daudi x Hela D98 (male x female) hybrids, DAD 1 and DAD 10, demonstrated even higher H-Y antigen levels comparable to that of normal male peripheral blood lymphocytes [5].
  • Here we use a GFP-tagged subunit of the OST complex (GFP-Dad1) that rescues the temperature-sensitive (ts) phenotype of tsBN7 cells, where Dad1 is degraded and N-glycosylation is inhibited, to study the lateral mobility of the TC by FRAP [6].
  • Overexpression of Dad1/PhCCD8 in the dad1-1 mutant complemented the mutant phenotype, and RNA interference in the wild type resulted in an increased branching phenotype [7].
  • Other differences in phenotype associated with the loss of Dad1/PhCCD8 function included altered timing of axillary meristem development, delayed leaf senescence, smaller flowers, reduced internode length, and reduced root growth [7].
  • DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase [8].
 

Biological context of DAD1

 

Anatomical context of DAD1

 

Associations of DAD1 with chemical compounds

  • A tomato lipase homologous to DAD1 (LeLID1) is induced in post-germinative growing stage and encodes a triacylglycerol lipase [16].
  • Both methods showed that tunicamycin induces apoptosis in wild-type BHK21 cells, similar to the defect of Dad1p [17].
  • * Background and Aims Evidence from pea rms1, Arabidopsis max4 and petunia dad1 mutant studies suggest an unidentified carotenoid-derived/plastid-produced branching inhibitor which moves acropetally from the roots to the shoots and interacts with auxin in the control of apical dominance [18].
 

Other interactions of DAD1

 

Analytical, diagnostic and therapeutic context of DAD1

  • Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells [23].
  • By means of a two-hybrid method involving DAD1 as bait, the C-terminal region of Mcl-1, one of the bcl-2 family, was isolated [13].
  • We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17 beta4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively [24].
  • Sequence analysis of the cDNA encoding the DAD1 homologue of A. ventricosus revealed that the 339-bp cDNA has an open reading frame of 113 amino acid residues [25].
  • Northern blot analysis shows that the transcripts of A. ventricosus DAD1 homologue gene are present in all tissues examined, suggesting that A. ventricosus DAD1 is expressed in most, if not all, body tissues [25].

References

  1. Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas. Tanaka, K., Kondoh, N., Shuda, M., Matsubara, O., Imazeki, N., Ryo, A., Wakatsuki, T., Hada, A., Goseki, N., Igari, T., Hatsuse, K., Aihara, T., Horiuchi, S., Yamamoto, N., Yamamoto, M. Biochim. Biophys. Acta (2001) [Pubmed]
  2. Quantitative expression of apoptosis-regulating genes in endometrium from women with and without endometriosis. Braun, D.P., Ding, J., Shaheen, F., Willey, J.C., Rana, N., Dmowski, W.P. Fertil. Steril. (2007) [Pubmed]
  3. Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. Patel, N.M., Nozaki, S., Shortle, N.H., Bhat-Nakshatri, P., Newton, T.R., Rice, S., Gelfanov, V., Boswell, S.H., Goulet, R.J., Sledge, G.W., Nakshatri, H. Oncogene (2000) [Pubmed]
  4. A novel human processed gene, DAD-R, maps to 12p12 and is expressed in several organs. Kuittinen, T., Eggert, A., Lindholm, P., Horelli-Kuitunen, N., Palotie, A., Maris, J.M., Saarma, M. FEBS Lett. (2000) [Pubmed]
  5. The HLA-dependent expression of testis- organizing H-Y antigen by human male cells. Beutler, B., Nagai, Y., Ohno, S., Klein, G., Shapiro, I.M. Cell (1978) [Pubmed]
  6. Active translocon complexes labeled with GFP-Dad1 diffuse slowly as large polysome arrays in the endoplasmic reticulum. Nikonov, A.V., Snapp, E., Lippincott-Schwartz, J., Kreibich, G. J. Cell Biol. (2002) [Pubmed]
  7. The Decreased apical dominance1/Petunia hybrida CAROTENOID CLEAVAGE DIOXYGENASE8 gene affects branch production and plays a role in leaf senescence, root growth, and flower development. Snowden, K.C., Simkin, A.J., Janssen, B.J., Templeton, K.R., Loucas, H.M., Simons, J.L., Karunairetnam, S., Gleave, A.P., Clark, D.G., Klee, H.J. Plant Cell (2005) [Pubmed]
  8. DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase. Kelleher, D.J., Gilmore, R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. The DAD1 protein, whose defect causes apoptotic cell death, maps to human chromosome 14. Yulug, I.G., See, C.G., Fisher, E.M., Ylug, I.G. Genomics (1995) [Pubmed]
  10. The highly conserved defender against the death 1 (DAD1) gene maps to human chromosome 14q11-q12 and mouse chromosome 14 and has plant and nematode homologs. Apte, S.S., Mattei, M.G., Seldin, M.F., Olsen, B.R. FEBS Lett. (1995) [Pubmed]
  11. Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes. Zhong, X.P., Krangel, M.S. J. Immunol. (1999) [Pubmed]
  12. DAD1 is required for the function and the structural integrity of the oligosaccharyltransferase complex. Sanjay, A., Fu, J., Kreibich, G. J. Biol. Chem. (1998) [Pubmed]
  13. A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1, one of the bcl-2 protein family. Makishima, T., Yoshimi, M., Komiyama, S., Hara, N., Nishimoto, T. J. Biochem. (2000) [Pubmed]
  14. Gene expression profile of endothelin-1-induced growth in glomerular mesangial cells. Mishra, R., Leahy, P., Simonson, M.S. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  15. Dopamine control of seizure propagation: intranigral dopamine D1 agonist SKF-38393 enhances susceptibility to seizures. Turski, W.A., Cavalheiro, E.A., Ikonomidou, C., Bortolotto, Z.A., Klockgether, T., Turski, L. Synapse (1990) [Pubmed]
  16. A tomato lipase homologous to DAD1 (LeLID1) is induced in post-germinative growing stage and encodes a triacylglycerol lipase. Matsui, K., Fukutomi, S., Ishii, M., Kajiwara, T. FEBS Lett. (2004) [Pubmed]
  17. Inhibition of N-linked glycosylation causes apoptosis in hamster BHK21 cells. Yoshimi, M., Sekiguchi, T., Hara, N., Nishimoto, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  18. A reappraisal of the role of abscisic Acid and its interaction with auxin in apical dominance. Cline, M.G., Oh, C. Ann. Bot. (2006) [Pubmed]
  19. Induction of apoptosis in prostatic tumor cell line DU145 by staurosporine, a potent inhibitor of protein kinases. Zhang, H., Hoang, T., Saeed, B., Ng, S.C. Prostate (1996) [Pubmed]
  20. Resistance of ex vivo expanded CD3+CD56+ T cells to Fas-mediated apoptosis. Verneris, M.R., Kornacker, M., Mailänder, V., Negrin, R.S. Cancer Immunol. Immunother. (2000) [Pubmed]
  21. Gene expression profiling in anaplastic large cell lymphoma and Hodgkin's disease. Trempat, P., Villalva, C., Xerri, L., Armstrong, F., Duplantier, M.M., Delsol, G., Brousset, P. Leuk. Lymphoma (2004) [Pubmed]
  22. Increased apoptosis in B-chronic lymphocytic leukemia cells as a result of cyclin D3 down regulation. Wang, P., Pavletic, Z.S., Joshi, S.S. Leuk. Lymphoma (2002) [Pubmed]
  23. Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells. Nakashima, T., Sekiguchi, T., Kuraoka, A., Fukushima, K., Shibata, Y., Komiyama, S., Nishimoto, T. Mol. Cell. Biol. (1993) [Pubmed]
  24. A molecular correlate to the Gleason grading system for prostate adenocarcinoma. True, L., Coleman, I., Hawley, S., Huang, C.Y., Gifford, D., Coleman, R., Beer, T.M., Gelmann, E., Datta, M., Mostaghel, E., Knudsen, B., Lange, P., Vessella, R., Lin, D., Hood, L., Nelson, P.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. cDNA cloning of a defender against apoptotic cell death 1 (DAD1) homologue, responsive to external temperature stimulus from the spider, Araneus ventricosus. Sik Lee, K., Hwa Chung, E., Hee Han, J., Dae Sohn, H., Rae Jin, B. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2003) [Pubmed]
 
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